Portal hemodynamics during nitroglycerin administration in cirrhotic patients

Nitroglycerin is a potent venous dilator and a mild arterial vasodilator that has been shown to improve the hemodynamic response to vasopressin in portal hypertensive patients and to decrease portal pressure in experimental animals. In order to determine the effect of nitroglycerin on portal venous hemodynamics, we studied 11 patients with alcoholic cirrhosis before and during the administration of sublingual nitroglycerin (0.4 and 0.6 mg). The hepatic venous pressure gradient (which was obtained by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure) decreased from 17.9 +/- 6.5 mm Hg (mean +/- S.D.) to 15.1 +/- 5.1 mm Hg (p less than 0.02) at the peak of the effect, which occurred from 2 to 12 min after nitroglycerin administration. The mean arterial pressure was reduced from 96 +/- 10 mm Hg to a peak decrease of 76 +/- 18 mmHg (p less than 0.001). The peak change in the hepatic venous pressure gradient induced by nitroglycerin correlated directly with the peak change in mean arterial pressure (r = 0.79, p less than 0.01). There was a moderate increase in heart rate in response to the decrease in blood pressure (73 +/- 15 to 83 +/- 15 beats per min, p less than 0.001). Two of the 11 patients did not reduce their hepatic venous pressure gradient after 0.6 mg nitroglycerin. Reductions in portal pressure were observed with both increases and moderate decreases in azygos blood flow, suggesting that, as observed in experimental animals, the portal-pressure-reducing effect of nitroglycerin could be due to two different and independent mechanisms, a reduction in portal blood flow or portal-collateral vasodilatation.     

Portohepatic Pressures, Hepatic Function, and Blood Gases in the Combination of Nitroglycerin and Vasopressin: Search for Additive Effects in Cirrhotic Portal Hypertension

We studied the effects of the combination of nitroglycerin and vasopressin on portohepatic hemodynamics, hepatic function, and blood gases in nine patients with cirrhosis and portal hypertension. Vasopressin infusion at a dose of 0.4 U/min caused a significant fall in portal pressure, which is evaluated by portal venous pressure gradient (-34%, p less than 0.01), associated with a decrease in hepatic perfusion (-33%, p less than 0.01) and intrinsic clearance (-20%, p less than 0.01) after 30 min. The arterial oxygenation, however, was not modified (paO2; from 73 +/- 8 to 72 +/- 7 mm Hg, NS). Nitroglycerin infusion at a dose of 100 micrograms/min was then administered for 20 min. The addition of nitroglycerin produced a further reduction in free portal venous pressure (-12%, p less than 0.01), but this was not associated with a significant improvement in both hepatic perfusion (+16%, NS) and intrinsic clearance (-7%, NS). In addition, there was a significant fall in arterial oxygenation (paO2; from 72 +/- 7 to 59 +/- 5 mm Hg, p less than 0.01). We conclude that the addition of nitroglycerin to vasopressin has a beneficial effect on free portal venous pressure, but does not have hepatic benefit. Moreover, sufficient care must be taken, when treating portal hypertension with this combination, to avoid arterial hypoxemia.     

Effects of somatostatin on hepatic and systemic hemodynamics in patients with cirrhosis of the liver: comparison with vasopressin

The effects of somatostatin on hepatic and systemic hemodynamics were investigated in 17 patients with chronic liver disease and severe portal hypertension during the hemodynamic assessment before elective portal-systemic shunt surgery. The injection of somatostatin (1.0 microgram/kg) caused a decrease of the wedged hepatic venous pressure, from 19.5 +/- SE 1.3 mmHg to 14.0 +/- 1.0 mmHg (p < 0.001). Injections of 0.5 and 2.0 microgram/kg had similar effects. During somatostatin infusion at a constant rate (7.5 microgram/min) there was a reduction of the wedged hepatic venous pressure (-17.0%, p < 0.001) and estimated hepatic blood flow (-17.5%, p < 0.01) but no significant changes in hepatic vascular resistance, cardiac output, systemic blood pressure, peripheral resistance, or cardiopulmonary pressures. In marked contrast to the selective action of somatostatin on splanchnic hemodynamics, vasopressin infusion (0.3 U/min) in 6 patients caused not only significant falls in the wedged hepatic venous pressure and estimated hepatic blood flow (-28.6% and -31.8%, respectively), but also significant changes in the systemic circulation, including a reduction of the cardiac output (-19.7%, p < 0.01) and heart rate (-12.6%, p < 0.01) and an increase of the arterial pressure (+18.8%, p < 0.01) and peripheral resistance (+46.8%, p < 0.01). These results show that somatostatin effectively reduces hepatic blood flow and portal pressure in patients with cirrhosis and severe portal hypertension, without altering the systemic circulation.     

Systemic and portal haemodynamic changes following triglycyllysine vasopressin plus nitroglycerin administration in patients with hepatitis B-related cirrhosis

We measured the haemodynamic changes following triglycyllysine vasopressin administration and after addition of nitroglycerin in twelve patients with portal hypertension due to hepatitis B-related cirrhosis. A bolus i.v. injection of triglycyllysine vasopressin at a dose of 2 mg reduced the hepatic venous pressure gradient from 18.5 +/- 3.7 (mean +/- S.D.) to 15.6 +/- 4.0 mmHg, p less than 0.001. However, the cardiac index decreased from 4.8 +/- 1.0 to 3.7 +/- 0.8 l/min m2, p less than 0.001; the heart rate decreased from 79 +/- 15 to 71 +/- 13, p less than 0.01; the right atrial pressure increased from 3.2 +/- 1.9 to 5.3 +/- 2.3 mmHg, p less than 0.001; the mean arterial pressure increased from 92 +/- 13 to 103 +/- 13 mmHg, p less than 0.05; and the systemic vascular resistance rose from 939 +/- 182 to 1367 +/- 310 dyn/s cm-5, p less than 0.001. Furthermore, both mean pulmonary arterial pressure and pulmonary capillary wedge pressure showed a significant increase following triglycyllysine vasopressin administration as compared with baseline values (p less than 0.005). The addition of sublingual nitroglycerin at a dose of 0.6 mg returned all the systemic haemodynamic parameters to baseline levels. On the other hand, nitroglycerin administration caused no further change in the hepatic venous pressure gradient. We concluded that although triglycyllysine vasopressin significantly reduced portal pressure in patients with hepatitis B-related cirrhosis, it produced untoward systemic haemodynamic changes similar to those seen with vasopressin. The addition of nitroglycerin improved the detrimental systemic haemodynamic effects produced by triglycyllysine vasopressin without further reducing the hepatic venous pressure gradient.     

Effects of vaso-active agents on hepatic function and blood gases in patients with cirrhosis: A study of vasopressin and nitroglycerin

The effects of vaso-active agents on hepatic function and splanchnic oxygenation were studied in 17 patients with cirrhosis and portal hypertension. Eight patients received vasopressin (0.3 iu/min) and nine patients received nitroglycerin (50 micrograms/min). Both drugs caused a significant reduction in the portal venous pressure gradient. Vasopressin infusion significantly decreased intrinsic clearance of indocyanine green (-23%, P less than 0.01). This may be due to a decreased hepatic perfusion (-28%, P less than 0.01) and portal venous oxygenation (-15% in portal venous oxygen tension, P less than 0.05). In contrast, no changes in hepatic perfusion and portal venous oxygenation were observed after nitroglycerin infusion. Nitroglycerin did not decrease intrinsic clearance of indocyanine green. These results suggest that vasodilators, rather than vasoconstrictors, might be welcome in the treatment of patients with cirrhosis and portal hypertension.     

Effects of glypressin on the splanchnic and systemic circulation in patients with cirrhosis

Although not demonstrated in patients with cirrhosis, it is generally claimed that administration of vasopressin in the form of triglycyl-lysine-vasopressin (glypressin) may prevent untoward systemic effects of this former hormone. The aim of this study was to assess the effects of intravenous administration of 2 mg of glypressin on splanchnic and systemic hemodynamics in 9 patients with cirrhosis under stable circulatory conditions. One hour after the injection, the following statistically significant changes were observed as compared to the baseline values (m +/- SEM): wedged hepatic venous pressure, -9 +/- 2 p. 100; hepatic venous pressure gradient, -16 +/- 3 p. 100; azygos blood flow, -24 +/- 6 p. 100; heart rate, -16 +/- 3 p. 100; cardiac index, -23 +/- 2 p. 100; systemic vascular resistances, +47 +/- 11 p. 100; wedged pulmonary arterial pressure, +44 +/- 15 p. 100. In conclusion, in patients with cirrhosis in a stable hemodynamic condition, intravenous administration of glypressin decreased portal venous pressure and blood flow into the superior portal systemic collateral circulation but did not prevent the untoward systemic hemodynamic effects of vasopressin.     

Development of tolerance to nitroglycerin in the arterial and venous circulation of dogs

The purpose of this study was to define the effects of nitroglycerin on venous tone and to investigate the time course of nitroglycerin tolerance in the peripheral circulation. The changes in the arterial and venous circulation resulting from an intravenous infusion of nitroglycerin (5 micrograms/kg per min) after 5 minutes (acute infusion) were compared with those changes that occurred after 2 hours (chronic infusion) of the same infusion in six splenectomized, ganglion-blocked dogs. Hemodynamics, blood volume and venous and arterial compliance were measured during each infusion. Nitroglycerin initially decreased mean arterial pressure from 81.5 +/- 2.0 to 57.6 +/- 2.7 mm Hg (p less than 0.01). Central blood volume decreased from 21.1 +/- 1.4 to 15.9 +/- 1.1 ml/kg (p less than 0.01), while total blood volume and unstressed vascular volume did not change. In the acute study, nitroglycerin increased venous compliance 33% from 1.75 +/- 0.14 to 2.32 +/- 0.16 ml/mm Hg per kg (p less than 0.01) and arterial compliance 33% from 0.049 +/- 0.007 to 0.065 +/- 0.007 ml/mm Hg per kg (p less than 0.01). At the end of the 2 hour infusion, arterial pressure increased and was now unchanged from control. Central blood volume had returned to baseline, 17.8 +/- 0.9 ml/kg. Total blood volume and unstressed vascular volume remained unchanged. With the long-term infusion, both arterial and venous compliance decreased (p less than 0.02) to 0.050 +/- 0.006 and 1.50 +/- 0.06 ml/mm Hg per kg, respectively, such that neither value was different from control. Nitroglycerin levels remained constant throughout.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of propranolol on hepatic and systemic hemodynamics in dogs with chronic bile duct ligation

Propranolol has been reported to reduce portal and wedged hepatic vein pressures in man and may be useful for the prevention of variceal bleeding. However, its mechanism of action remains unclear. We have examined the effect of propranolol on the systemic and hepatic circulations in dogs with chronic bile duct ligation and secondary biliary cirrhosis. Under anesthesia, eight dogs received four increasing doses of propranolol as an i.v. bolus followed by continuous infusion. Systemic and hepatic hemodynamic parameters were measured in basal conditions and after a 30 min infusion for each dose. Portal vein and hepatic artery blood flows were measured with electromagnetic flow meters. All dogs had portal hypertension (portal venous pressure 15.3 +/- 0.8 mm Hg), a hyperdynamic circulation and severe liver disease resulting in a marked decrease of propranolol systemic clearance (8.75 ml per min per kg) and extraction (40%). The first dose of propranolol induced a decrease in heart rate (-27%) and in cardiac index (-21%), and an increase in systemic vascular resistance (+20%). With increasing doses, the systemic vascular resistance decreased with an increase in the cardiac index. Propranolol was not associated with significant modifications of hepatic hemodynamics: portal, wedged and free hepatic venous pressures and hepatic artery blood flow were stable, and portal blood flow decreased slightly at very high propranolol levels. In seven dogs studied without dissection of the hepatic vessels, there was a small decrease in portal pressure, but not in wedged and free hepatic venous pressures with increasing doses of propranolol. Thus, in dogs with intrahepatic portal hypertension, propranolol has significant effects on systemic hemodynamics, but only minimal effects on the hepatic circulation.     

Chronic bile duct ligation in the dog: hemodynamic characterization of a portal hypertensive model

Splanchnic and systemic hemodynamics were measured in six normal dogs and in 18 dogs that had the bile ducts ligated for a period of 8 weeks. In the bile duct-ligated dogs, there was a decrease in arterial pressure (110 +/- 4 mm Hg vs. normal 136 +/- 6 mm Hg; p less than 0.005) and peripheral vascular resistance (4.60 +/- 0.38 vs. 6.28 +/- 0.38 dynes-sec-cm-5; p less than 0.02), and an increase in cardiac index (129 +/- 7 vs. 98 +/- 9 ml per min per kg; p less than 0.05). The splanchnic hemodynamic characteristics in the bile duct-ligated dogs included an increase in portal venous pressure (13.3 +/- 0.6 mm Hg vs. 6.7 +/- 0.5 mm Hg; p less than 001) and wedged hepatic venous pressure (14 +/- 1.2 mm Hg), the development of extensive portal-systemic shunting (49 +/- 10 vs. 0.03 +/- 0.01%; p less than 0.01), and a decrease in portal venous flow (194 +/- 21 ml per min vs. 427 +/- 21 ml per min; p less than 0.001). This study demonstrated that chronic bile duct-ligated dogs develop sinusoidal portal hypertension with extensive portal-systemic shunting and a hyperdynamic systemic circulation. These findings closely resembled hemodynamic abnormalities observed in human cirrhosis and suggest that this model is useful in physiopathological and pharmacological studies of portal hypertension.     

The effect of nitroglycerin on pulmonary vascular capacitance in dogs

In this study we investigated the hypothesis that the decrease in pulmonary vascular pressures observed after administration of nitroglycerin is in part due to a shift in the pulmonary vascular pressure-volume relationship. The experiments were done in six closed-chest dogs anesthetized with pentobarbital, in which pulmonary, cardiac, and intestinal relative blood volumes were determined by equilibrium blood pool scintigraphy. Nitroglycerin (30 micrograms/kg/min) caused 7% (p less than 0.02) and 12% (p less than 0.02) reductions in pulmonary and total cardiac blood volume, respectively, and a 7% (p less than 0.01) increase in intestinal blood volume. This shift of blood from the heart and the pulmonary circulation to the systemic (intestinal) circulation was accompanied by reductions in mean pulmonary artery pressure from 16 +/- 2 mm Hg to 12 +/- 1 mm Hg (p less than 0.01), in mean pulmonary capillary wedge pressure from 11 +/- 2 mm Hg to 6 +/- 1 mm Hg (p less than 0.01), and in mean portal pressure from 9 +/- 1 mm Hg to 8 +/- 1 mm Hg (p less than 0.01). The position of the pulmonary vascular pressure-blood volume relationship was unaffected by nitroglycerin, whereas the portal pressure-intestinal blood volume relationship was shifted to the left and upward. These changes suggest that pulmonary vascular tone remained unchanged, whereas intestinal vascular tone decreased during administration of nitroglycerin. In conclusion, nitroglycerin decreased pulmonary vascular pressures through a passive emptying of the pulmonary circulation as a result of increased systemic (intestinal) vascular capacitance.     

Effects of vasopressin on the intravariceal pressure in patients with cirrhosis: comparison with the effects on portal pressure

The present study investigated to what extent measurements of wedged and free hepatic venous pressures adequately reflect the effects of vasopressin at the esophageal varices in patients with cirrhosis. Eleven patients undergoing therapeutic sclerotherapy were studied by measuring wedged hepatic venous pressure, intravariceal pressure, free hepatic venous pressure, superior vena cava pressure and the intravascular pressure gradients wedged hepatic venous pressure-free hepatic venous pressure and intravariceal pressure-superior vena cava pressure, prior to and after vasopressin injection (1 IU, iv). Vasopressin caused a significant reduction in intravariceal pressure (from 22.5 +/- 9.4 to 19.2 +/- 8.4 mm Hg, p less than 0.001). Measurement of wedged hepatic venous pressure and free hepatic venous pressure closely reflected the reduction in variceal pressure. Thus, wedged hepatic venous pressure decreased by 16 +/- 11%, which is close to the 14 +/- 7% change in intravariceal pressure, and the 23 +/- 12% fall in the pressure gradient wedged hepatic venous pressure-free hepatic venous pressure was mirrored by the 26 +/- 10% change in intravariceal pressure-superior vena cava pressure. These pressure gradients decreased more than the absolute pressures (intravariceal pressure and wedged hepatic venous pressure) due to concomitant increases in superior vena cava pressure (1.9 +/- 1.9 mm Hg) and free hepatic venous pressure (0.6 +/- 1.9 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of the administration of terlipressin alone or combined with nitroglycerin in patients with cirrhosis]

Terlipressin (Glypressin), a synthetic analog of vasopressin, induces arteriolar vasoconstriction which causes both a portal hypotensive effect and certain side-effects on the systemic circulation (elevated arterial pressure and reduced cardiac output). The combination of nitroglycerin with terlipressin might accentuate the portal hypotensive effect and prevent the side-effects on the systemic circulation. The aim of this study was to examine the systemic and splanchnic hemodynamic responses to terlipressin administered alone or combined with nitroglycerin in patients with cirrhosis. Systemic and splanchnic hemodynamics were measured before and 1 h after a bolus of terlipressin (1 to 2 mg IV) given alone (n = 10) or in association with nitroglycerin infusion (25 micrograms/min, n = 9). Terlipressin alone significantly increased the arterial pressure by 21%, systemic vascular resistance by 60%, and significantly decreased cardiac output by 23%. The right atrial and pulmonary pressures significantly increased and the wedged hepatic venous pressure and hepatic venous pressure gradient significantly decreased by 8% and 16%, respectively. The combined therapy decreased the cardiac output by 20%, but did not significantly modify the other systemic and splanchnic hemodynamic values. No significant differences were found between terlipressin and the combined therapy concerning changes in wedged hepatic venous pressure or hepatic venous pressure gradient. We conclude that in patients with cirrhosis, nitroglycerin prevents the deleterious vasoconstrictor and vasopressor effects of terlipressin. However, the combined therapy, as terlipressin alone, decreases the cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodynamic response to intravenous vasopressin and nitroglycerin in portal hypertension.

We have evaluated the haemodynamic effects of intravenous (iv) nitroglycerin (NG) and vasopressin (VP) alone and in combination, in 12 patients with cirrhosis and recent variceal haemorrhage (two to seven days). Nitroglycerin infusion alone (200 micrograms/min) produced a significant fall in portal pressure (WHVP-FHVP) (from 16.4 (0.6) to 13.3 (1.2) mmHg; p less than .001) associated with hypotension (mean arterial pressure from 95 (7) to 78 (9) mmHg; p less than 0.005). Vasopressin alone (0.4 IU/min) reduced portal pressure (20.7 (1.3) to 14.0 (1.3) mmHg; p less than 0.001), but there was considerable variation in the systemic haemodynamic changes with increased cardiac output in four of six patients. The combination of vasopressin and nitroglycerin corrected all systemic haemodynamic disturbances produced by either agent alone. This combination led, however, to a further reduction in portal pressure (from 13.7 (0.9) to 11.7 (0.7) mmHg p less than 0.01). These results show that: (1) intravenous nitroglycerin reduces portal pressure, and (2) the combination of nitroglycerin and vasopressin reverses systemic haemodynamic disturbances produced by either agent alone and leads to a further decrease in portal pressure.     

Nicardipine Infusion Improved Hepatic Function But Failed to Reduce Hepatic Venous Pressure Gradient in Patients with Cirrhosis

We investigated the effects of nicardipine on systemic and splanchnic hemodynamics and on liver function in 16 patients with cirrhosis and portal hypertension. Patients received a continuous infusion of 0.3 mg/min of nicardipine (n = 10) and a control infusion (n = 6). No significant changes were observed after a control infusion. In contrast, systemic vasodilatation, evidenced by a significant fall in mean arterial pressure (-14%, p less than 0.01) and systemic vascular resistance (-30%, p less than 0.01), increased heart rate (+8%, p less than 0.01) and cardiac output (+21%, p less than 0.01), and increased hepatic blood flow (+43%, p less than 0.01) were observed at 60 min after a continuous infusion of nicardipine. Although nicardipine improved hepatic function (intrinsic clearance from 0.29 +/- 0.13 to 0.33 +/- 0.15 L/min, p less than 0.05), portal pressure evaluated by hepatic venous pressure gradient was not reduced significantly (from 16.3 +/- 4.9 to 15.1 +/- 5.7 mm Hg; NS). We conclude that a continuous infusion of nicardipine improves liver function but has no beneficial effect on portal pressure in patients with cirrhosis.     

The effect of the combination of nitroglycerin and propranolol on splanchnic and systemic hemodynamics in a portal hypertensive rat model

Present investigations support major contributions from increases in both portal blood flow and portal vascular resistance in the mechanism that maintains portal hypertension. beta-Adrenergic blockers have been shown to reduce the elevated portal blood flow component. The possibility that nitroglycerin administration could reduce the elevated portal vascular resistance component is investigated here. Portal hypertension was induced in rats by a calibrated constriction of the portal vein. Portal hypertensive rats receiving placebo exhibited significant (p less than 0.05) elevations over normal rats receiving placebo in cardiac index, portal venous inflow and portal pressure. Portal hypertensive rats were then divided into groups receiving nitroglycerin infusion, propranolol (beta-adrenergic blockade) and combined administration of nitroglycerin and propranolol. Significant reductions (p less than 0.05) in portal blood flow of 30, 32 and 44%, respectively, were accompanied by significant portal pressure reductions of 2.7 +/- 0.2, 1.7 +/- 0.3 and 3.6 +/- 0.4 mm Hg in all groups, respectively (p less than 0.05). Nitroglycerin failed to prevent a 46% rise in portal-collateral resistance accompanying the portal blood flow reduction, similar to resistance rises also found in propranolol-treated (33%) and combination nitroglycerin-propranolol-treated (49%) groups. We conclude that nitroglycerin infusion can significantly reduce portal pressure, alone or in combination with beta-blockade, by reducing portal venous inflow. It appears that nitroglycerin reduces portal blood flow through the effect of baroreceptor sympathetic reflexes that constrict the splanchnic bed in response to vasodilatation and venous pooling.     

Low dose of nitroglycerin failed to improve splanchnic hemodynamics in patients with cirrhosis: evidence for an impaired cardiopulmonary baroreflex function

High doses of nitroglycerin may decrease portal pressure in patients with cirrhosis with untoward effects such as arterial hypotension and a decrease in systemic O2 uptake. In the present study, low doses of nitroglycerin (7 to 15 micrograms per min, i.v.) were administered in 11 patients with cirrhosis in order to unload cardiopulmonary baroreceptor--one of the possible mechanisms by which nitroglycerin may improve splanchnic hemodynamics--and moreover to avoid deleterious systemic effects. Nitroglycerin significantly decreased right atrial pressure (-35%) and pulmonary wedged pressure (-27%) with significant increase in plasma norepinephrine concentration (+23%), which indicated that cardiopulmonary baroreceptor unloading was achieved. Changes in systemic hemodynamics were slight, although significant, with a decrease in arterial pressure (-8%) and an increase in heart rate (+8%); this indicates a minimal effect on high-pressure baroreflexes. In contrast, no significant change was observed in hepatic venous pressure gradient, hepatic blood flow and azygos blood flow. However, the fraction of cardiac output reaching the azygos system significantly increased by 18%. Plasma renin activity did not change significantly. Moreover, O2 transport and uptake were significantly decreased. These findings show that low doses of nitroglycerin failed to improve splanchnic hemodynamics in patients with cirrhosis. These results suggest an impaired cardiopulmonary baroreflex function which is probably located on the efferent arch.     

Vasopressin and vasopressin plus nitroglycerin for portal hypertension. Effects on systemic and splanchnic hemodynamics and coronary blood flow

We measured the coronary, systemic, and splanchnic effects of vasopressin and vasopressin plus nitroglycerin in 8 stable patients with alcoholic cirrhosis. Vasopressin (0.1-0.8 U/min) increased pressure in the hepatic vein, pulmonary artery and pulmonary capillaries. Wedged hepatic (portal) vein pressure was unchanged; the hepatic venous pressure gradient (wedged-free hepatic vein pressure) fell. Insignificant declines occurred in cardiac output, gastroesophageal collateral (azygous) blood flow, hepatic blood flow and coronary sinus (cardiac) blood flow. The addition of nitroglycerin (40-70 micrograms/min) reduced pressure in the hepatic vein, pulmonary artery and pulmonary capillaries, while increasing the hepatic venous pressure gradient. Wedged hepatic vein pressure did not change. Gastroesophageal collateral (azygous) flow increased markedly; cardiac output rose to a lesser degree. Coronary sinus and hepatic blood flow did not change. Nitroglycerin ameliorated the increases in systemic and pulmonary artery pressure produced by vasopressin but also tended to reverse the decline in the hepatic venous pressure gradient and markedly increased gastroesophageal flow. Neither drug significantly affected coronary blood flow.     

Hemodynamic effects of a combination of vasopressin and ketanserin in patients with hepatitis b-related cirrhosis.

We measured the hemodynamic effects of intravenous vasopressin, ketanserin (a 5-hydroxytryptamine-2 receptor blocker), and vasopressin plus ketanserin in 33 patients with hepatitis B-related cirrhosis. Thirteen patients received vasopressin alone (0.66 units/min), ten patients ketanserin alone (10 mg), and ten patients vasopressin followed by vasopressin plus ketanserin. Vasopressin alone reduced the hepatic venous pressure gradient (from 18 +/- 5, mean +/- S.D., to 9 +/- 3 mmHg, p less than 0.0001) and cardiac output (p less than 0.0001), but increased mean arterial pressure (p less than 0.005), mean pulmonary arterial pressure (p less than 0.0001), pulmonary capillary wedge pressure (p less than 0.0001), and systemic vascular resistance (p less than 0.001). There was no significant change in heart rate. Ketanserin alone produced a significant fall in the hepatic venous pressure gradient (from 16 +/- 4 to 13 +/- 3 mmHg, p less than 0.0001), mean arterial pressure (p less than 0.005), mean pulmonary arterial pressure (p less than 0.005), and pulmonary capillary wedge pressure (p less than 0.005). Heart rate, cardiac output, and systemic vascular resistance were not significantly changed. The addition of ketanserin to vasopressin corrected most of the systemic hemodynamic disturbances produced by vasopressin. This combination did not lead to a further reduction in the hepatic venous pressure gradient. We conclude that intravenous ketanserin reduces portal pressure in patients with hepatitis B-related cirrhosis. The addition of ketanserin to vasopressin improves the detrimental systemic hemodynamic effects of vasopressin without further reducing the portal pressure.     

Effect of intraportal nitroglycerin on portosystemic hemodynamics in patients with cirrhosis: comparison with i.v. route

We observed 18 patients with portal hypertension and cirrhosis to compare the effects of intraportal nitroglycerin on portosystemic hemodynamics with the i.v. route. Patients received 1 microgram/kg/min of nitroglycerin intravenously (n = 9) or the same dose of nitroglycerin directly into the portal vein (n = 9). Both routes of nitroglycerin significantly reduced mean arterial pressure and this effect was higher with the i.v. route (-28.0% versus -19.3%, p less than 0.02). The portal pressure, as evaluated by the portal venous pressure gradient or hepatic venous pressure gradient, was also reduced significantly in both groups. The fall in portal pressure was higher in the intraportal group, but the difference was not significant (intravenous versus intraportal, -23.9 versus -25.1% in portal venous pressure gradient, -25.2 versus -33.4% in hepatic venous pressure gradient). The hepatic blood flow was maintained despite the significant reduction in portal pressure by both routes. These results indicate that intraportal nitroglycerin decreases portal pressure with a smaller effect on systemic hemodynamics than the i.v. route. We conclude that the oral administration of nitroglycerin, which is a pathway equivalent to the intraportal route, may be more useful than the i.v. (i.e., sublingual) route in the treatment of portal hypertension.     

Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis.

In order to examine the relationship of various haemodynamic parameters in two different liver diseases, 10 patients with cirrhosis of liver and 14 patients with non-cirrhotic portal fibrosis were studied. In cirrhotics, mean (+/- SD) wedged hepatic (25.8 +/- 6.4 mmHg), intrahepatic (24.5 +/- 6.2 mmHg) and intrasplenic (25.0 +/- 5.6 mmHg) pressures correlated significantly (p less than 0.001) with intravariceal (25.2 +/- 6.7) pressure measurements. In patients with NCPF, mean (+/- SD) wedged hepatic (9.1 +/- 3.7 mmHg) and intraphepatic (15.4 +/- 5.8 mmHg) pressures were significantly (p less than 0.01) lower than the intrasplenic (24.5 +/- 4.2 mmHg) and intravariceal (23.96 +/- 5.6 mmHg) pressures. Two independent pressure gradients, one between intrasplenic and intrahepatic pressure (8.9 +/- 6.5 mmHg) and another between intrahepatic and wedged hepatic venous pressure (6.2 +/- 5.6 mmHg) were seen in non-cirrhotic portal fibrosis patients, indicating the likelihood of both pre- and perisinusoidal resistance to flow of portal venous blood in these patients. A highly significant (p less than 0.001) correlation between intravariceal and intrasplenic pressures was found in patients with cirrhosis of liver (r = 0.93), as well as in patients with non-cirrhotic portal fibrosis (r = 0.85). No correlation was found between the size of oesophageal varices and wedged hepatic and intrahepatic pressures. Patients with grade 4 varices had significantly higher intravariceal (p less than 0.01) and intrasplenic (p less than 0.05) pressure than patients with grade 2 varices. It can be concluded that intravariceal pressure is representative of portal pressure in patients with cirrhosis of liver as well as in non-cirrhotic portal fibrosis patients and it can be recommended as the single haemodynamic investigation in patients with portal hypertension and oesophageal varices.